The long-term goal of the research proposed herein is to understand the underlying neural logic of dopaminergic modulation of animal behavior. Dopamine modulation of synaptic plasticity is central to the molecular and cellular mechanisms underlying behavioral alterations associated with drug addiction. A great deal of progress has been made in understanding how dopamine alters synaptic activity in certain regions of the brain. However, less is known about how dopamine targets multiple regions of the brain and coordinates behavioral changes in intact neural circuits and organisms. In the nematode Caenorhabditis elegans, we have found that chemosensory avoidance behavior, which utilizes AMPA/kainate-like glutamate receptors for excitatory neurotransmission, is modulated by dopamine. Based on the expression patterns of the dopamine and glutamate receptors involved, dopaminergic input to the neural circuit that drive this behavior likely occurs at multiple cellular foci. This behavior in C. elegans thus serves as a model for understanding how dopamine functions systemically at multiple sites of action to modulate animal behavior. My specific aims are: (1) To precisely characterize the expression and site of action of dopamine receptors in the well-characterized chemosensory avoidance neural circuit of C. elegans;and (2) To determine how dopamine regulates glutamatergic signaling at sensory to interneuron synapses in this neural circuit. These studies will provide insight into how modulatory neurotransmitters such as dopamine globally affect behavioral circuits. 1 PUBLIC HEALTH RELEVANCE: Addictive drugs affect the signaling activity of the neurotransmitter dopamine. We propose to study how dopamine signaling affects behavior in the model organism Caenorhabditis elegans. This organism has a simple and well- characterized nervous system that allows us to examine the role of dopamine from molecular and genetic to neural and behavioral effects.